The ultimate goals of the Center are to improve drug therapy and decrease the toxicity of drugs, economic poisons and other xenobiotics through a better understanding of the mechanisms governing their biotransformation and disposition. Many xenobiotics are biotransformed and this almost always terminates their action and facilitates their excretion. Biotransformation therefore figures prominantly among the factors that determine the usefulness or toxicity of drugs and other foreign compounds. Biotransformation of xenobiotics is mostly dependent upon the hepatic microsomal cytochrome P-450-dependent systems. Our research is concerned with the characterization of these systems in the liver and other organs, with developmental aspects of these systems in the fetus and neonate, with the interaction of these systems with other microsomal systems, and with environmental factors which may influence the amounts and kinds of these systems in various organs. We believe that a better understanding of the microsomal cytochrome P-450 systems will lead to a better understanding of the biotransformation of xenobiotics and that this will contribute substantially to the realization of our ultimate goals - the improvement of drug therapy and the mitigation of the toxicity of drugs and other xenobiotics. Progress during the past year can be categorized under seven headings: 1) Use of linoleic acid hydroperoxide in the characterization of membrane bound cytochrome P-450 systems; 2) Stoichiometry of cytochrome P-450-dependent reactions; 3) Contribution of a "soluble" factor to cytochrome P-450-dependent reactions; 4) Characterization of extrahepatic cytochrome P-450 systems; 5) Developmental aspects of cytochrome P-450 systems; 6) Immunochemical approaches to the study of cytochrome P-450 systems; 7) Depressant action of interferon inducing agents on cytochrome P-450 systems. BIBLIOGRAPHIC REFERENCES: G.J. Mannering, Role of Cytochrome b5 in the NADH synergism of NADPH-dependent reactions of the cytochrome P-450 monooxygenase system of hepatic microsomes. Adv. Exper. Med. Biol. 58, 405 (1976). $